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The protective effect of female gender on the development of albuminuria in a polygenetic rat model is further enhanced by replacement of a major autosomal QTL.

Authors: Schulz, A  Schlesener, M  Weiss, J  Hansch, J  Wendt, N  Kossmehl, P  Grimm, D  Vetter, R  Kreutz, R 
Citation: Schulz A, etal., Clin Sci (Lond). 2007 Oct 22;.
Pubmed: (View Article at PubMed) PMID:17953514
DOI: Full-text: DOI:10.1042/CS20070300

Clinical and experimental studies indicate that the progression of renal disease is faster in males than females. These observations are corroborated by a sexual dimorphism observed in the polygenetic Munich Wistar Fromter (MWF) rat model. The age dependent spontaneous progression of increased urinary albumin excretion (UAE) in male MWF is influenced by multiple quantitative trait loci (QTL). In contrast, female MWF develop only a slight increase in UAE, while the role of genetic factors for this phenotype is unknown. Here we show that compared to resistant spontaneously hypertensive rats (SHR) both male and female MWF develop a significant increase in UAE at 24 weeks of age (p<0.0001, respectively), although blood pressures are lower compared to SHR (p<0.0001). UAE is significantly higher in male (7fold) compared to female MWF (162.6+/-15.9 vs. 24.0+/-5.5 mg/24h, p<0.0001) and only male MWF develop significant glomerulosclerosis and tubulointerstitial damage in the kidney (p<0.0001). To test the role of genetic factors for the development of low grade albuminuria in female MWF we analyzed the role of a major UAE QTL on rat chromosome 6. To this end we analyzed a consomic MWF-6 SHR strain in which chromosome 6 from SHR was introgressed into the MWF background. Time course analysis of UAE in females indicated that the mild increase of UAE in MWF was fully suppressed by exchange of rat chromosome 6. Thus, taken together with previous studies in males we show that RNO6 protects against the increase of albuminuria with age in both female and male MWF.

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CRRD Object Information
CRRD ID: 1642911
Created: 2007-11-01
Species: All species
Last Modified: 2007-11-01
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.